Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children19610.24287/1726-1708-2018-17-3-85-92CLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯTarget therapy of cherubism in a 9 years old childТаргетная терапия херувизма у ребенка 9 летhttps://orcid.org/0000-0003-0043-9059LopatinA. V.ЛопатинА. В.
Russian Federation
https://orcid.org/0000-0002-6881-7709KugushevA. Yu.КугушевА. Ю.
Russian Federation

Alexander Y. Kugushev, PhD, plastic surgeon, pediatric surgeon, Department of Maxillofacial Surgery

119571, Moscow, Leninsky рrosp., 117

Кугушев Александр Юрьевич, канд. мед. наук, врач пластический хирург, детский хирург, отделение челюстно-лицевой хирургии РДКБ 

119571, Москва, Ленинский просп., 117 

drkugushev@gmail.comhttps://orcid.org/0000-0003-0319-3103YasonovS. A.ЯсоновС. А.
Russian Federation
Peoples' Friendship University of RussiaФГАОУ ВО «Российский университет дружбы народов»Russian National Research Medical University named after N.I. PirogovФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова»2409201817385922409201824092018Copyright ©; 2018, «D. Rogachev NMRCPHOI»Copyright ©; 2018, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2018«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/196

Reparative giant cell granulomas (RGCG) is a rare benign lesion of the skull bones in children, which is 1.7% of all recorded cases of RGCG. Despite the benign nature of the disease, RGCG often recurs after surgical treatment and can metastasize. One of the rare forms of RGCG is cherubism, characterized by total defeat of the upper and lower jaw, in connection with which it is impossible to carry out radical surgical treatment, especially in children in the period before puberty. In the department of maxillofacial surgery of the Russian Childrens’ Clinical Hospital under ambulatory supervision for 3 years was a child diagnosed with cherubism. During this time, progressive growth of the upper and lower jaw persisted, leading to exorbitalism. After the histological verification of the diagnosis and the approval of the ethical committee, a course of therapy with the drug denosumab was conducted. Histological examination of the tumor denosumab treatment showed a significant response which resulted in disappearance of giant cells. CT before and after the therapy showed an increase in bone density from 65 to 385 HU. The size of tumor nodes reduced, allowing to made contour resection of the mandible. The structure and volume of the upper jaw reached the average value and did not require surgical correction. After the course of the denosumab, there was no growth retardation according to the control X-ray examination of the wrist. inoperable forms of RGCG and cherubism, a complex approach is needed, including a course of denosumab therapy followed by transfer to therapy with alendronic acid. After the therapy, contour resection of excess bone tissue is possible with the purpose of medical and social rehabilitation of such patients.

giant cell reparative granulomacherubismdenosumabchildrenalendronic acidbisphosphonatesгигантоклеточная репаративная гранулемахерувизмденозумабдетиалендроновая кислотабисфосфонаты1. Jaffe H.L. Giant-cell reparative granuloma, traumatic bone cyst, and fibrous (fibro-osseous) dysplasia of the jawbones. Oral Surg Oral Med Oral Pathol 6: 159; 1953.Jaffe H.L. Giant-cell reparative granuloma, traumatic bone cyst, and fibrous (fibro-osseous) dysplasia of the jawbones. Oral Surg Oral Med Oral Pathol 6: 159; 1953.2. Hyckel P., Berndt A., Schleier P., Clement J.H., Beensen V., Peters H., Kosmehl H. Cherubism-new hypothesis on pathogenesis and therapeutic consequences. J Cranio-Maxillofac Surg 2005; 33 (1): 61–8.Hyckel P., Berndt A., Schleier P., Clement J.H., Beensen V., Peters H., Kosmehl H. Cherubism-new hypothesis on pathogenesis and therapeutic consequences. J Cranio-Maxillofac Surg 2005; 33 (1): 61–8.3. Lo B., Faiyaz-Ul-Haque M., Kennedy S., Aviv R., Tsui L.C., Teebi A.S. Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Am J Med Genet A 2003; 121A (1): 37–40.Lo B., Faiyaz-Ul-Haque M., Kennedy S., Aviv R., Tsui L.C., Teebi A.S. Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 causes cherubism. Am J Med Genet A 2003; 121A (1): 37–40.4. Meng X.M., Yu S.F., Yu G.Y. Clinico-pathological study of 24 cases of cherubism. Int J Oral Max Surg 2005; 34 (4): 350–6.Meng X.M., Yu S.F., Yu G.Y. Clinico-pathological study of 24 cases of cherubism. Int J Oral Max Surg 2005; 34 (4): 350–6.5. Anderson D.E., McClendon J.L. Cheru-bism-hereditary fibrous dysplasia of the jaws; I genetic considerations. Oral Surg Oral Med Oral Pathol 1962; 15 (Suppl 2): 5–16.Anderson D.E., McClendon J.L. Cheru-bism-hereditary fibrous dysplasia of the jaws; I genetic considerations. Oral Surg Oral Med Oral Pathol 1962; 15 (Suppl 2): 5–16.6. Tiziani V., Reichenberger E., Buzzo C.L., Niazi S., Fukai N., Stiller M., Peters H., et al. The gene for cherubism maps to chromosome 4h16. Am J Hum Genet 1999; 65: 158–66.Tiziani V., Reichenberger E., Buzzo C.L., Niazi S., Fukai N., Stiller M., Peters H., et al. The gene for cherubism maps to chromosome 4h16. Am J Hum Genet 1999; 65: 158–66.7. Ueki Y., Tiziani V., Santanna C., Fukai N., Maulik C., Garfinkle J., Ninomiya C., et al. Reichenberger E. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet 2001; 28: 125–6.Ueki Y., Tiziani V., Santanna C., Fukai N., Maulik C., Garfinkle J., Ninomiya C., et al. Reichenberger E. Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism. Nat Genet 2001; 28: 125–6.8. O'Connell J.E., Bowe C., Murphy C., Toner M., Kearns G.J. Aggressive giant cell lesion of the jaws: A review of management options and report of a mandibular lesion treated with denosumab. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120: e191.O'Connell J.E., Bowe C., Murphy C., Toner M., Kearns G.J. Aggressive giant cell lesion of the jaws: A review of management options and report of a mandibular lesion treated with denosumab. Oral Surg Oral Med Oral Pathol Oral Radiol 2015; 120: e191.9. Skubitz K.M., Cheng E.Y., Clohisy D.R., Thompson R.C., Skubitz A.P. Gene expression in giant-cell tumors. J Lab Clin Med 2004; 144: 193–200.Skubitz K.M., Cheng E.Y., Clohisy D.R., Thompson R.C., Skubitz A.P. Gene expression in giant-cell tumors. J Lab Clin Med 2004; 144: 193–200.10. Rutkowski P.I., Ferrari S., Grimer R.J., Stalley P.D., Dijkstra S.P., Pienkowski A., et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol 2015; 22 (9): 2860–8.Rutkowski P.I., Ferrari S., Grimer R.J., Stalley P.D., Dijkstra S.P., Pienkowski A., et al. Surgical downstaging in an open-label phase II trial of denosumab in patients with giant cell tumor of bone. Ann Surg Oncol 2015; 22 (9): 2860–8.11. Branstetter D.G., Nelson S.D., Manivel J.C., Blay J.Y., Chawla S., Thomas D.M., et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 2012; 18: 4415–24.Branstetter D.G., Nelson S.D., Manivel J.C., Blay J.Y., Chawla S., Thomas D.M., et al. Denosumab induces tumor reduction and bone formation in patients with giant-cell tumor of bone. Clin Cancer Res 2012; 18: 4415–24.12. Karras N.A. Denosumab Treatment of Metastatic Giant-Cell Tumor of Bone in a 10-Year-Old Girl. J Clin Oncol 2013 Apr 20; 31 (12): e200–e202.Karras N.A. Denosumab Treatment of Metastatic Giant-Cell Tumor of Bone in a 10-Year-Old Girl. J Clin Oncol 2013 Apr 20; 31 (12): e200–e202.13. Kobayashi E., Setsu N. Osteosclerosis induced by denosumab.Lancet 2015 Feb 7; 385 (9967): 539.Kobayashi E., Setsu N. Osteosclerosis induced by denosumab.Lancet 2015 Feb 7; 385 (9967): 539.14. Bredell M., Rordorf T., Kroiss S., Rücker M., Fritz Zweifel D., Rostetter C. Denosumab as a Treatment Alternative for Central Giant Cell Granuloma: A Long-Term Retrospective Cohort Study. J Oral Maxillofac Surg 2017: 1–10.Bredell M., Rordorf T., Kroiss S., Rücker M., Fritz Zweifel D., Rostetter C. Denosumab as a Treatment Alternative for Central Giant Cell Granuloma: A Long-Term Retrospective Cohort Study. J Oral Maxillofac Surg 2017: 1–10.15. Balke M., Ahrens H., Streitbuerger A., Koehler G., Winkelmann W., Gosheger G., Hardes J. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 2009; 135: 149–58.Balke M., Ahrens H., Streitbuerger A., Koehler G., Winkelmann W., Gosheger G., Hardes J. Treatment options for recurrent giant cell tumors of bone. J Cancer Res Clin Oncol 2009; 135: 149–58.16. Thomas D., Henshaw R., Skubitz K., Chawla S., Staddon A., Blay J.Y., et al. Denosumab in patients with giant-cell tumour of bone: An openlabel, phase 2 study. Lancet Oncol 2010; 11: 275–80.Thomas D., Henshaw R., Skubitz K., Chawla S., Staddon A., Blay J.Y., et al. Denosumab in patients with giant-cell tumour of bone: An openlabel, phase 2 study. Lancet Oncol 2010; 11: 275–80.17. Lipton A., Jacobs I. Denosumab: Benefits of RANK ligand inhibition in cancer patients. Curr Opin Support Palliat Care 2011; 5: 258–64.Lipton A., Jacobs I. Denosumab: Benefits of RANK ligand inhibition in cancer patients. Curr Opin Support Palliat Care 2011; 5: 258–64.18. Rostetter C., Rordorf T., Essig H., Zweifel D., Schumann P., Rücker M., Bredell M. New approach to treatment of giant granula with denosumab. A case example. Swiss Dent J 2017; 127: 520 (in German).Rostetter C., Rordorf T., Essig H., Zweifel D., Schumann P., Rücker M., Bredell M. New approach to treatment of giant granula with denosumab. A case example. Swiss Dent J 2017; 127: 520 (in German).19. Tarsitano A., Del Corso G., Pizzigallo A., Marchetti C. Aggressive central giant cell granuloma of the mandible treated with conservative surgical enucleation and interferon-alpha-2a: Complete remission with long-term follow-up. J Oral Maxillofac Surg 2015; 73: 2149.Tarsitano A., Del Corso G., Pizzigallo A., Marchetti C. Aggressive central giant cell granuloma of the mandible treated with conservative surgical enucleation and interferon-alpha-2a: Complete remission with long-term follow-up. J Oral Maxillofac Surg 2015; 73: 2149.20. Naidu A., Malmquist M.P., Denham C.A., Schow S.R. Management of central giant cell granuloma with subcutaneous denosumabtherapy. J Oral Maxillofac Surg 2014; 72: 2469.Naidu A., Malmquist M.P., Denham C.A., Schow S.R. Management of central giant cell granuloma with subcutaneous denosumabtherapy. J Oral Maxillofac Surg 2014; 72: 2469.21. Schreuder W.H., Coumou A.W., Kessler P.A., de Lange J. Alternative pharmacologic therapy for aggressive central giant cell granuloma:Denosumab. J Oral Maxillofac Surg 2014; 72: 1301.Schreuder W.H., Coumou A.W., Kessler P.A., de Lange J. Alternative pharmacologic therapy for aggressive central giant cell granuloma:Denosumab. J Oral Maxillofac Surg 2014; 72: 1301.22. Gupta B., Stanton N., Coleman H., White C., Singh J. A novel approach to the management of a central giant cell granuloma with denosumab: A case report and review of current treatments. J Craniomaxillofac Surg 2015; 43: 1127.Gupta B., Stanton N., Coleman H., White C., Singh J. A novel approach to the management of a central giant cell granuloma with denosumab: A case report and review of current treatments. J Craniomaxillofac Surg 2015; 43: 1127.23. Pham Dang N., Longeac M., Picard M., Devoize L., Barthélémy I. Central giant cell granuloma in children: Presentation of different therapeutic options.Rev Stomatol Chir Maxillofac Chir Orale 2016; 117: 142 (in French).Pham Dang N., Longeac M., Picard M., Devoize L., Barthélémy I. Central giant cell granuloma in children: Presentation of different therapeutic options.Rev Stomatol Chir Maxillofac Chir Orale 2016; 117: 142 (in French).24. Skubitz K.M. Giant cell tumor of bone: current treatment options. Curr Treat Options Oncol 2014; 15: 507.Skubitz K.M. Giant cell tumor of bone: current treatment options. Curr Treat Options Oncol 2014; 15: 507.25. Ruggiero S.L., Dodson T.B., Fantasia J., Goodday R., Aghaloo T., Mehrotra B., O'Ryan F. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw – 2014 Update. J Oral Maxillofac Surg 2014; 72: 1938.Ruggiero S.L., Dodson T.B., Fantasia J., Goodday R., Aghaloo T., Mehrotra B., O'Ryan F. American Association of Oral and Maxillofacial Surgeons position paper on medication-related osteonecrosis of the jaw – 2014 Update. J Oral Maxillofac Surg 2014; 72: 1938.26. Saad D., Saad P. Report of a jaw osteonecrosis possibly caused by denosumab. Eur J Oral Implantol 2017;10 (2): 213–22.Saad D., Saad P. Report of a jaw osteonecrosis possibly caused by denosumab. Eur J Oral Implantol 2017;10 (2): 213–22.27. Demirel F., Esen I., Tunc B., Tavil B. Scarcity despite wealth: Osteopetrorickets. J Pediatr Endocrinol Metab 2010; 23: 931–4.Demirel F., Esen I., Tunc B., Tavil B. Scarcity despite wealth: Osteopetrorickets. J Pediatr Endocrinol Metab 2010; 23: 931–4.